DESCRIPTION (Adapted from the Abstract): The investigator proposes to characterize the genomic region of human chromosome 19 that contains the Killer Cell Inhibitory Receptor (KIR) genes. These gene products are expressed in Natural Killer cells, an immune cell population with cytolytic capability. Presently, it is understood that a number of cell surface molecules can either activate or inhibit the cytolytic responses of this cell population. The KIR molecules, upon engaging their ligands, class I major histocompatibility molecules, produce an inhibitory affect. Public databases contain DNA sequences for more than 35 KIR molecules and neighbor-joining analysis places these distinct sequences into 5-7 groups. It has been suggested, by the investigator's laboratory as well as others, that these groups correspond to genes and members within a group correspond to alleles. The specific aims are to delineate the size of this KIR complex, map it by multi-complete digests, number the genes contained within the complex, and inspect for proximal regulatory elements. DNA clones that derive from the relevant region of chromosome 19, as deduced from preliminary radiation hybrid mapping experiments, are freely obtainable from several genome centers. The clones will be tested for KIR sequences by hybridization and positive clones mapped by multi-enzyme complete digests. Contig gaps will be filled by sequencing 5' and 3' regions, synthesizing oligonucleotides and screening prospective linking clones with polymerase chain reaction. DNA sequencing experiments of upstream flanking regions will determine the presence of putative regulatory motifs. Natural Killer cells are suggested to play an important role in the elimination of neoplastic cells that attempt to evade immune lysis by reducing cell surface expression of class I major histocompatibility molecules. Although cellular experiments have provided much insight into the influences of cell surface molecules on cytolytic activity, it is proposed that a firm description of the KIR genomic complex will enable a more precise analysis of this large group of related molecules.